This proposal requests continued support for the Einstein Aging Study (EAS), a multi-disciplinary Program Project with a productive 16-year history. In the current proposal, our longitudinal research expands to emphasize screening for and definitive diagnosis of early Alzheimer's disease (AD) and preclinical AD in a population-based sample of community- residing older adults. As OD becomes a treatable disease, early identification has become an important public health objective. Identifying individuals with preclinical AD will provide a basis for preventative trials and ultimately a basis for public health initiatives in AD prevention. This proposal also focuses on identifying the neuroanatomical and neurochemical changes associated with early AD, preclinical AD and healthy aging. Removing individuals with pre-clinical AD from normative samples is essential for characterizing age-related cognitive decline. Clinical differentiation of healthy aging and pre- clinical AD is also an essential prerequisite for differentiating the neuropathologic changes of healthy aging from those of dementia. We propose to achieve our interdisciplinary research goals through three closely integrated research Projects supported by four interdependent Cores. Project 1 (Screening), a new project, proposes to validate novel telephone screening methods for detecting AD and preclinical AD in a population-based sample. Project 2 (Preclinical) focuses on the diagnosis of preclinical AD and on the mechanisms of changes in memory in normal elderly, preclinical AD and diagnosable AD. Project 3 (Clinical-Pathologic Correlations) emphasizes the structural neurochemical and immunologic changes in the brain in AD, preclinical AD and healthy aging. The Projects are linked by the interrelated research themes, by a shared sample of well-characterized study participants recruited in Project 1 from the Health Care Financing Administration list, and by the Statistical Core which integrates information gathered by all three projects as well as the Clinical and Neuropathologic Cores. New and innovative screening and diagnostic measures, more precise neuropathologic procedures, and systematic community-based sampling will result in increased sensitivity and specificity in the identification of A and preclinical disease, critical to the eventual development of preventative interventions.